"Stable" inertial cavitation.

This note compares theoretical predictions of pressure waves scattered by free gas bubbles with recent acoustical determinations of cavitation thresholds for individual microbubbles of the surfactant-stabilized contrast agent Sonazoid(R). The results indicate that surfactant-coated microbubbles undergo "stable" (i.e., repetitive) inertial cavitation above a threshold of 0.3 to 0.4 MPa at 2.5 MHz, and that irreversible postcollapse bubble fragmentation usually requires much higher pressures (approximately 1.5 MPa). Adverse bioeffects can be expected in vivo far below these fragmentation pressures when contrast agents are present. With diagnostically relevant exposures, the threshold for the generation of petechiae in skeletal muscle is approximately 0.6 MPa at 2.5 MHz.

Sudden infant death syndrome and secretin treatment for autism.

The Back to Sleep Campaigns remain the greatest influence on the reduction of sudden infant death syndrome. Blatt and Meguid review updates on the effectiveness of these campaigns in reducing sudden infant death syndrome. They also review studies on why parents do not follow this proven advice. The contribution of the risks of other environmental factors are also reviewed. Also discussed are commentaries from a study reviewed last on the link between a prolonged QT electrocardiogram interval and sudden infant death syndrome. Church provides a cogent and timely review of the reported effectiveness of hormone secretin effectiveness in treating children with autism. This newly proposed treatment has been in the spotlight of the lay public, the popular media, and the scientific community. In short order, secretin as a treatment for autism has moved from a chance observation to the subject of a double-blind, placebo-controlled study.

Sudden infant death syndrome, child sexual abuse, and child development.

Since the introduction of the Back to Sleep Campaigns, there has been a dramatic reduction in sudden infant death syndrome in this country. Steven Blatt and Victoria Meguid review the literature surrounding sleep position. Investigators have continued efforts to find other modifiable risk factors of sudden infant death syndrome. A prospective study of more than 33,000 neonates found a link between a prolonged QT electrocardiogram interval and sudden infant death syndrome. Also discussed are investigations seeking to explain the relationship between smoking and sudden infant death syndrome. Ann Botash, Florence Jean-Louis and Mongkae Ploy Siripornsawan review the latest thinking on genital warts and their relation to specific viral etiologies and child sexual abuse. Other symptoms and signs of sexual abuse are the focus of a number of articles that can help the practitioner care for these unfortunate children. Catherine Church reviews medication options for children diagnosed with pervasive developmental disorders or autism spectrum disorders. Finally, in this article, risperidone, fluoxetine and naltrexone are reviewed.

Home-based developmental screening of children in foster care.

Children in foster care have a high prevalence of developmental delay. A program for developmental screening was designed to address the increased risk of developmental delay among children in foster care. Fifty-two children birth to 18 months were evaluated using the Denver Developmental Screening Test-II (DDST-II), Early Language Milestone Scale-2 (ELM-2), and the HOME Scale. Forty-nine children were screened with the Infant Neurological International Battery. Thirty five percent of the children failed DDST-II screening. Language assessment with the ELM-2 resulted in a mean global ELM-2 standard score of 89. Sixty-one percent of children had abnormal neurologic INFANIB screening exams. HOME scores reflected foster care environments that provided adequate developmental and emotional stimulation for the children. Implications for future interventions should move from developmental screening to comprehensive developmental testing and expansion of foster parent education regarding the growth and development of the foster children in their care.

A comprehensive, multidisciplinary approach to providing health care for children in out-of-home care.

Every community has children placed in the out-of-home care system. Despite a high prevalence of health, mental health, and developmental morbidity in children in care, most child welfare agencies have not provided adequate diagnostic and therapeutic services for these children. A comprehensive, multidisciplinary clinic for children in out-of-home care involving pediatrics, child psychology, nursing, child development, and child welfare is described. Profiles of the health, mental health, and developmental status of the children in out-of-home care are also presented.

Re-evaluation of the concept that high cell concentrations "protect" cells in vitro from ultrasonically induced lysis.

Diminution of apparent ultrasonic cell lysis in vitro with increasing cell concentration/volume fraction has often been observed. A substantial fraction of the cells may be lysed by ultrasound at low cell concentrations, but only a few percent are lysed when the concentration is a fraction of that of whole blood. This suggests that sonolysis of cells in vitro is suppressed by high cell concentrations, and, therefore, that sonolysis of cells in vivo is unlikely. We present the results of a retrospective analysis of experimental data and a theoretical analysis; these indicate that while relative sonolytic yield declines with increasing cell concentration, the "absolute" extent of ultrasound-induced lysis remains large. We find evidence that in vitro sonolysis of cells is limited at high cell densities by the number of available microbubbles and/or the number of cells each bubble may encounter and lyse prior to bubble "inactivation." Theory indicates the latter arises in consequence to the cell concentration-dependent formation of cell aggregates around pulsating bubbles.

Child abuse, sudden infant death syndrome, and attention-deficit hyperactivity disorder.

A review of recent literature helps to clarify normal variations in the physical examination of children who are thought to have been sexually abused. In many instances, no abnormal physical findings are discovered. Clinicians must continue to pay careful attention to the history and work with other professionals to implement appropriate management, despite the lack of physical findings. Guidelines for evaluating sudden and unexpected infant deaths are reviewed. The current recommendations of the American Academy of Pediatrics for infant sleep positions are discussed in light of epidemiologic studies in the United States and other countries. Attention-deficit hyperactivity disorder appears to respond best to a combination of stimulant medication, parent training in coping with behavior of affected children, and social skill training for the affected children themselves. A review of recent research failed to reach consistent correlations between resistance to thyroid hormone and attention-deficit hyperactivity disorder.

The high-functioning autistic experience: birth to preteen years.

A retrospective chart review of 15 children with high-functioning autism was conducted for the years 1981 through 1992. The purpose of the study was to describe the experience of children with high-functioning autism from infancy through preadolescence. Chart data included clinic staff records, parent letters, academic program records, service records, and comments from the children themselves. The findings of this study support the proposition that children with autism who have an IQ above 70 follow a varied but improving course over time. All 15 children met the DSM-III-R criteria for autism when first evaluated. By middle elementary school, however, none of the children in this study met the DSM-III-R criteria for autism, although they continued to have various language disturbances, social skill deficits, and unique behavioral qualities.

Lysis of erythrocytes by exposure to CW ultrasound.

The threshold for lysis of erythrocytes suspended at concentrations of 0.5-1% in saline or plasma in rotating cylindrical exposure vessels is approximately spatial peak intensities of 2 W/cm2 at 1 MHz continuous wave (CW). Results of a series of experiments in which cell concentration, viscosity and gas composition of the suspending medium and rotation speed of the exposure vessel were varied combined with observations of sonoluminescence are all consistent with a hypothesis that cells are lysed by inertial (transient) acoustic cavitation. For the proposed mechanism to operate in cell suspensions, it is necessary that bubbles be brought into contact with the cells. Rotation of the chamber recycles bubbles that are driven by radiation forces to the far wall of the chamber in a matter of milliseconds. The physical and chemical properties of the wall of the chamber appear to be important as stabilizing sites for nuclei that serve as seeds for cavitation events.

The acoustic filter: an ultrasonic blood filter for the heart-lung machine.

Cardiopulmonary bypass-associated encephalopathy is thought to be due in part to continuous microembolization of the brain with gas microbubbles more than 40 microns in diameter during bypass. Current barrier filter technology cannot effectively remove such small microbubbles in fragile fluids such as blood. The design concepts for a new nonbarrier ultrasound-based fluid filtration system (an "acoustic filter") capable of filtering small microbubbles from blood are presented. The acoustic filter uses a field of high-intensity ultrasound to push microbubbles down an acoustic gradient, where they can be collected and removed. To test the filtration efficiency of the system, a Doppler ultrasound bubble detector was built. By monitoring the prefilter and postfilter Doppler signal an assessment of filtration efficiency was made. A suspension of stable albumin-encapsulated microbubbles (4 to 32 microns) were used as a model of the microbubble contaminants that might be found in the arterial return line of the heart-lung machine. Inactivated, the acoustic filter neither removed nor added microbubbles to the fluid. Activated, the acoustic filter provided total or near-total clearing of microbubbles. We conclude that the acoustic filter can remove microbubbles from a cardiopulmonary bypass-like apparatus.

Acoustic cavitation produced by microsecond pulses of ultrasound: a discussion of some selected results.

Because of its extensive utilization in clinical practice, and because the subjects examined are often fragile and sensitive to trauma, the safety of diagnostic ultrasound has always been of concern. Of the various mechanisms through which ultrasound could act in a manner deleterious to a patient, acoustic cavitation, should it occur, appears to possess significant potential for biological damage. This paper reviews several recent reports of progress by our two groups and demonstrates the conditions under which cavitation has been observed by microsecond pulses of ultrasound. Although these results give no indications that diagnostic ultrasound may pose a true risk to a patient, they do indicate that in vivo cavitation may occur under certain conditions.

Confirmation of an ultrasound-induced mutation in two in-vitro mammalian cell lines.

In-vitro V79 and L5178Y cells were exposed in a rotating test tube to continuous-wave (CW) 1 MHz 35 W/cm2 ultrasound (0-4 or 0-3 min, respectively) and subsequently assayed for mutation as evidenced by resistance to 6-thioguanine (6-TG). There was a modest but statistically significant increase in mutation frequency in both cell types with increase in ultrasound exposure duration. X-ray exposures (3-9 Gy, a "positive control") yielded a large increase in 6-TG resistance. The data support an earlier report by Kaufman (1985) of an ultrasound-induced increase in mutation to 6-TG resistance in in-vitro mammalian cells.

Time lapse and microscopic examinations of insonated in vitro cells.

A fibroblast cell line (Balb/c 3T3) was sham/exposed to ultrasound (2.2 MHz resonant frequency, 35.4 W/cm2 SPTP, 3 microseconds pulse duration, 200 Hz prf) for 30 min and subsequently scored for cell motility and alterations in cell morphology. Cell motility was assessed by computerized tracking of cells. Cell morphology ("normal" or "abnormal") was determined blindly by three independent scorers. A positive control (1-4 Gy) yielded statistically significant alterations in cell motility and morphology; no such differences were observed for the ultrasound regimen. The results thus fail to confirm an earlier report by Liebeskind et al. (Brit. J. Cancer 45(Suppl. V):176-186; 1982) of ultrasound-induced alterations in cell motility and morphology.

Confirmation of the protective effect of cysteamine in in vitro ultrasound exposures.

Armour and Corry (Radiat. Res. (1982) 89 369-380) reported that ultrasound-induced damage to in vitro Chinese hamster ovary cells was significantly reduced in the presence of cysteamine. The objective of this study was to attempt verification of this result. Four series of experiments were undertaken using in vitro cell suspensions, namely: (1) determination of the effect of cysteamine concentration on cell growth; (2) determination of the temperature dependence of ultrasonically induced cell damage; (3) determination of a dose-response relationship for the cytotoxicity of cysteamine; and (4) assessment of cell integrity and reproductive capacity in the presence or absence of cysteamine during ultrasonic exposure. Ultrasound parameters included a resonance frequency of 1 MHz, a continuous wave exposure duration of 5 min, and intensities from 0 to 21.6 W cm-2. The results indicated a dependence of ultrasound's efficacy on the medium's temperature during insonation and a significant reduction of ultrasound efficacy in compromising cellular integrity in the presence of cysteamine.

A theoretical study of cavitation generated by an extracorporeal shock wave lithotripter.

The intense acoustic wave generated at the focus of an extracorporeal shock wave lithotripter is modeled as the impulse response of a parallel RLC circuit. The shock wave consists of a zero rise time positive spike that falls to 0 at 1 microsecond followed by a negative pressure component 6 microseconds long with amplitudes scaled to +1000 and -160 bars, P+ and P-, respectively. This pressure wave drives the Gilmore-Akulichev formulation for bubble dynamics; the zero-order effect of gas diffusion on bubble response is included. The negative pressure component of a 1000-bar shock wave will cause a preexisting bubble in the 1- to 10-microns range to expand to over 100 times its initial size, R0, for 250 microseconds, with a peak radius of approximately 1400 microns, then collapse very violently, emitting far UV or soft x-ray photons (black body). Gas diffusion does not appreciably mitigate the amplitude of the pressure wave radiated at the primary collapse, but does significantly reduce the collapse temperature. Diffusion also increases the bubble radius from R0 up to 40 microns and extends the duration of ringing following the primary collapse, assuming that the bubble does not break up or shed microbubbles. Results are sensitive to P+/P- and to the duration of the negative pressure cycle but not to rise time.

Sister chromatid exchanges in Chinese hamster ovary cells exposed to high intensity pulsed ultrasound: inability to confirm previous positive results.

This study was undertaken in an attempt to determine a physical mechanism of action for a recently published report of a small but statistically significant increase in sister chromatid exchanges (SCEs) in Chinese hamster ovary cells exposed to high-intensity pulsed ultrasound. The "positive" report's protocol involved a sizeable chance of ultrasound beam impingement on the side wall of the cell exposure chamber. Ten experiments per regimen were conducted; the regimens included exposures of (a) chamber center, (b) chamber wall, (c) nine grid sites, 0.5 mm between sites, and (d) nine grid sites, 1.5 mm between sites. The last was an exact replication of the conditions previously reported to induce the small SCE effect. The results did not support the postulate of an increase in SCEs with the ultrasound exposures.

Nonmonotonic behavior of the maximum collapse pressure in a cavitation bubble.

Calculations which are relevant to the determination of the maximum collapse pressure generated inside a microbubble as a function of peak pressure in the driving ultrasonic pulse are presented. It is found that above the threshold for transient cavitation, the maximum collapse pressure has a nonmonotonic variation. This result is explained on the basis of phase differences between the external applied acoustic pulse and the resulting bubble response.

An explanation for the decrease in cell lysis in a rotating tube with increasing ultrasound intensity.

Previous observations indicate that for in vitro mammalian cells insonated in rotating test tube the amount of cell lysis initially increases to some maximum and then decreases with further increase in ultrasound exposure. The results of the present investigation support the postulate that the reduction in cell lysis with increase in ultrasound intensity is related to the development of an ultrasonically induced "cloud" of bubbles in the fluid between the transducer and test tube; these bubbles mitigate against acoustic transmission thus reducing cell lysis in the insonated test tube.

Erratum: transient pulsations of small gas bubbles in water [J. Acoust. Soc. Am. 84, 985-998 (1988)] [corrected and republished].

Transient behavior of small gas bubbles in a liquid set into violent motion by ultrasonic pressure waves is of interest because of widespread use of microsecond pulses in diagnostic ultrasound. Such pulses contain only a few pressure cycles and the transient pulsations of bubbles set in motion by such pulses would determine the bubble-ultrasound interaction. A computer study has been made to obtain a global representation of the pulsation amplitudes R (t) of small gas bubbles (nuclei) in water during the first few cycles of a cw ultrasonic pressure. One objective was to obtain a better understanding of cavitation phenomena where many nuclei with initial radii Rn from 0.1-20 microns are set in motion at pressures ranging from 0.5-5 bars and at frequencies from 0.5-10 MHz. Results allowed construction of surfaces showing the relative bubble amplitude R/Rn as a function of Rn and of the time t/TA, where TA is the acoustic period. One finding is that, in the range of peak pressures found in diagnostic pulses, transient cavities would be generated during the first pressure cycle from nuclei with initial radii as small as a few microns (micron). Nuclei that grow into transient cavities in the first pressure cycle are here called "prompt" nuclei. At a specified pressure, the size range of radii Rn in which they occur decreases with increasing frequency. At 5 bars, the range of Rn for prompt nuclei is 0.166-11.35 microns at 0.5 MHz and vanishes at 10 MHz.